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三维生物打印胶原蛋白/丝素蛋白支架联合神经干细胞促进脊髓损伤后神经再生。

Three-dimensional bioprinting collagen/silk fibroin scaffold combined with neural stem cells promotes nerve regeneration after spinal cord injury.

作者信息

Jiang Ji-Peng, Liu Xiao-Yin, Zhao Fei, Zhu Xiang, Li Xiao-Yin, Niu Xue-Gang, Yao Zi-Tong, Dai Chen, Xu Hui-You, Ma Ke, Chen Xu-Yi, Zhang Sai

机构信息

Department of Thoracic Surgery, General Hospital of People's Liberation Army (PLA), Beijing; Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Chinese People's Armed Police Force (PAP) Medical Center, Tianjin, China.

Tianjin Key Laboratory of Neurotrauma Repair, Institute of Traumatic Brain Injury and Neuroscience, Center for Neurology and Neurosurgery of Chinese People's Armed Police Force (PAP) Medical Center; Tianjin Medical University, Tianjin, China.

出版信息

Neural Regen Res. 2020 May;15(5):959-968. doi: 10.4103/1673-5374.268974.

Abstract

Many studies have shown that bio-scaffolds have important value for promoting axonal regeneration of injured spinal cord. Indeed, cell transplantation and bio-scaffold implantation are considered to be effective methods for neural regeneration. This study was designed to fabricate a type of three-dimensional collagen/silk fibroin scaffold (3D-CF) with cavities that simulate the anatomy of normal spinal cord. This scaffold allows cell growth in vitro and in vivo. To observe the effects of combined transplantation of neural stem cells (NSCs) and 3D-CF on the repair of spinal cord injury. Forty Sprague-Dawley rats were divided into four groups: sham (only laminectomy was performed), spinal cord injury (transection injury of T10 spinal cord without any transplantation), 3D-CF (3D scaffold was transplanted into the local injured cavity), and 3D-CF + NSCs (3D scaffold co-cultured with NSCs was transplanted into the local injured cavity. Neuroelectrophysiology, imaging, hematoxylin-eosin staining, argentaffin staining, immunofluorescence staining, and western blot assay were performed. Apart from the sham group, neurological scores were significantly higher in the 3D-CF + NSCs group compared with other groups. Moreover, latency of the 3D-CF + NSCs group was significantly reduced, while the amplitude was significantly increased in motor evoked potential tests. The results of magnetic resonance imaging and diffusion tensor imaging showed that both spinal cord continuity and the filling of injury cavity were the best in the 3D-CF + NSCs group. Moreover, regenerative axons were abundant and glial scarring was reduced in the 3D-CF + NSCs group compared with other groups. These results confirm that implantation of 3D-CF combined with NSCs can promote the repair of injured spinal cord. This study was approved by the Institutional Animal Care and Use Committee of People's Armed Police Force Medical Center in 2017 (approval No. 2017-0007.2).

摘要

许多研究表明,生物支架在促进脊髓损伤后的轴突再生方面具有重要价值。事实上,细胞移植和生物支架植入被认为是神经再生的有效方法。本研究旨在制备一种具有模拟正常脊髓解剖结构腔隙的三维胶原/丝素蛋白支架(3D-CF)。这种支架可允许细胞在体外和体内生长。以观察神经干细胞(NSCs)与3D-CF联合移植对脊髓损伤修复的影响。将40只Sprague-Dawley大鼠分为四组:假手术组(仅行椎板切除术)、脊髓损伤组(T10脊髓横断损伤,未进行任何移植)、3D-CF组(将3D支架移植到局部损伤腔隙)和3D-CF+NSCs组(将与NSCs共培养的3D支架移植到局部损伤腔隙)。进行了神经电生理学、影像学、苏木精-伊红染色、嗜银染色、免疫荧光染色和蛋白质印迹分析。除假手术组外,3D-CF+NSCs组的神经学评分显著高于其他组。此外,在运动诱发电位测试中,3D-CF+NSCs组的潜伏期显著缩短,而波幅显著增加。磁共振成像和扩散张量成像结果显示,3D-CF+NSCs组的脊髓连续性和损伤腔隙填充情况均最佳。此外,与其他组相比,3D-CF+NSCs组再生轴突丰富,胶质瘢痕形成减少。这些结果证实,3D-CF与NSCs联合植入可促进脊髓损伤的修复。本研究于2017年获得武警部队医疗中心实验动物管理与使用委员会批准(批准号:2017-0007.2)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5972/6990792/c6cafd3f6496/NRR-15-959-g002.jpg

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